An examination of glial cells at aging neuromuscular junctions is proposed. One of the hallmarks of aging in humans is a loss of muscle fibers and, consequently, a loss of muscle strength. The loss of muscle fibers appears to be due to a failure of aging fibers to successfully regenerate following mechanical damage. Failure of muscle regeneration has been attributed to a failure of the regenerating fibers to become innervated. The glial or Schwann cells that cover the neuromuscular junction have recently been shown to play a major role in the repair and maintenance of neuromuscular junctions. These cells induce and guide nerve growth through the processes they extend in response to perturbations in muscle innervation. Moreover, activation of the Schwann cells at neuromuscular junctions can dramatically perturb the synaptic connection. Therefore it appears that age-related changes in Schwann cells could underlie some of the changes in muscle innervation. To examine this possibility, it is proposed to determine how the number and morphology of terminal Schwann cells is altered in aging rat muscle. Preliminary results suggest that as junctions age they gain Schwann cells. However, the junctions are also growing in size and it may be this increase in size rather than aging per se that leads to addition of Schwann cells. To examine this we will shrink and expand the size of fibers (and thus the junctions made upon them) in androgen-sensitive muscles in male rats by castration and testosterone administration. When muscles of the same age, but different size are compared, it should be possible to determine whether age or size determines the number of Schwann cells. We will also examine the responsiveness of Schwann cells at aging junctions to denervation, partial denervation, and muscle paralysis. These are conditions which in young adult animals lead to the growth of Schwann cell processes that promote nerve growth and repair of innervation. We will determine whether there are any deficiencies in the growth of Schwann cells in aging rat muscle. The results of this pilot study should provide evidence concerning the involvement of synaptic glial cells in the aging process.